Fear behaviors, which serve to protect the organism from dangers, can become maladaptive during mental illness. As amygdala is responsible for control of fear behaviors, we are trying to understand how its synaptic properties relate to its fear-regulating functions. The key amygdala property is high activity of its inhibitory neurons and low activity of its excitatory cells. As a result, the inhibition prevails in the amygdala preventing unnecessary defensive responses. In pathological states characteristic of fear and anxiety the balance between inhibition and excitation is shifted towards excitation, which leads to exaggerated defensive responses and fear generalization. The shift is thought to result mainly from alteration in the activity of amygdala interneuronal network, but mechanisms of this alteration are not known. We investigate these mechanisms by combining behavioral and physiological approaches. At behavioral level, we are developing model of amygdala disinhibition by aversive behavioral experiences. At physiological level, we analyze basic functions of amygdala inhibitory network. The ultimate goal is to bridge behavioral and physiological studies and determine which basic inhibitory mechanisms are altered following aversive behavioral experiences. During the last fiscal year we completed a study where a novel mechanism of the amygdala inhibitory dominance had been discovered using mice with green fluorescent protein (GFP) labeled inhibitory neurons. We found that the inputs to amygdala interneurons were potentiated much easier than the input to principal neurons. Furthermore, during such stimulation, the inputs in principal neurons were strongly inhibited via presynaptic GABAb-receptor, whereas inputs to interneurons were not. The mechanism responsible for this preferential recruitment of GABAb receptors on inputs to principal neurons was differential release of extrasynaptic GABA in the vicinity of principal neurons and interneurons. Our current efforts are to examine how this inhibitory mechanism is modulated during amygdala disinhibition by aversive experiences. To this end, we have established a behavioral procedure which enhances auditory fear conditioning and increases fear generalization. These changes are believed to depend on the amygdala. To further investigate amygdala interneuronal network, we began characterization of two transgenic lines of mice, in which specific subpopulations of interneurons are labeled with GFP. The first line expresses GFP under the control of promoter for the serotonin receptor 3 (5-HTr3) gene, and the second line has GFP under the control of the promoter of vasoactive intestinal peptide gene (VIP). These tools will allow us electrophysiological analysis of interaction between subpopulations of amygdala interneurons and changes of such interactions during amygdala disinhibition by aversive experiences.